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The goals of this study were to develop compounds that were selective and highly efficacious agonists at alpha-7 receptors, while varying in antagonist activity; and to test the hypothesis that these compounds had memory-related and neuroprotective actions associated with both agonist and antagonist alpha-7 receptor activities. Three compounds were(More)
The ideas and findings in this report should not be construed as an official DoD position. It is published in the interest of scientific and technical information exchange. Use of any trademarks in this report is not intended in any way to infringe on the rights of the trademark holder. Internal use. Permission to reproduce this document and to prepare(More)
The alpha7 nicotinic receptor agonist 3-[2,4-dimethoxybenzylidene]anabaseine (DMXB; GTS-21) was investigated for its ability to: (1) activate a variety of nicotinic receptor subtypes in Xenopus oocytes; (2) improve passive avoidance and spatial Morris water task performances in mecamylamine-sensitive manners in bilaterally nucleus basalis lesioned rats; and(More)
The nicotinic alpha7 agonist dimethoxybenzilidene anabaseine (DMXB) and cholinesterase inhibitor tetrahydroaminoacridine (THA) were investigated in a trans-synaptic model for neocortical atrophy and degeneration following nucleus basalis lesions. Bilateral lesions reduced parietal neuronal density in layers II-V 8 months later. DMXB administered i.p. daily(More)
MicroRNAs (miRNAs) play important roles in cancer development. By cloning and sequencing of a HPV16(+) CaSki cell small RNA library, we isolated 174 miRNAs (including the novel miR-193c) which could be grouped into 46 different miRNA species, with miR-21, miR-24, miR-27a, and miR-205 being most abundant. We chose for further study 10 miRNAs according to(More)
Two small-interfering RNAs (siRNAs) targeting alpha-synuclein (alpha-syn) and three control siRNAs were cloned in an adeno-associated virus (AAV) vector and unilaterally injected into rat substantia nigra pars compacta (SNc). Reduction of alpha-syn resulted in a rapid (4 week) reduction in the number of tyrosine hydroxylase (TH) positive cells and striatal(More)
While activation of alpha7 nicotinic receptors protects neurons from a variety of apoptotic insults in vitro, little is known about this neuroprotective action in vivo, especially under amyloidogenic conditions that mimic Alzheimer's disease. We therefore investigated the effects of 4OH-GTS-21, a selective partial agonist for these receptors, on(More)
Viral vector-mediated gene transfer in brain can provide a means for gene therapy and functional studies. However, robust and persistent transgene expression in specific populations of the adult brain has been difficult to achieve. In an attempt to produce localized and persistent transduction in rat brain, we compared recombinant adeno-associated virus(More)
Accumulation of human wild-type (wt) α-synuclein (α-syn) induces neurodegeneration in humans and in experimental rodent models of Parkinson disease (PD). It also leads to endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR). We overexpressed glucose regulated protein 78, also known as BiP (GRP78/BiP), to test the(More)
A population of neuronal cell bodies and their fiber pathways have been elucidated within the ovine hypothalamus. The immunoreactive neurons were located in the anterior and dorsal hypothalamus interspersed throughout the paraventricular nucleus. These perikarya were only observed when an antiserum that was generated against the C-terminal of CRF was(More)